Controlled Ovarian Hyperstimulation for PCOS

ByByOsama Abdalmageed, MDOsama Abdalmageed, MD

Assiut University ART UnitAssiut University ART Unit20172017

This presentation will try to cover: Introduction: PCOS, COH COH in PCOS is challenging The Prospective Hyperresponders Individualized COH (iCOH) in PCOS Success for PCOS in IVF Which Protocol?!

The starting doseGnRH Agonist For Pituitary DownregulationGnRH Antagonist For Pituitary DownregulationAdvantages of the Antagonist Downregulation in the

HyperrespondersCriteria for triggering of ovulation in COHGnRH agonist trigger protocolStrategies to prevent OHSSGnRH antagonist to abort OHSS

IntroductionPCOS

Common 8-25%

70% infertile.

Rotterdam criteria, 2004.

Lines of infertility ttt, ASRM,2007.

COH in PCOS is Challenging! WHY?! Initial poor response. Later sudden exaggerated “explosive”

response. High risk to develop OHSS. (life

threatening condition)? Immature oocytes, Fertilization rate,

Cleavage rate, Implantation rate, Multiple pregnancies, Miscarriage rate, Birth weight,

The Prospective Hyperresponders: age < 30 years PCO patient (> 24 antral follicles present

on baseline ultrasound examination), high number of AFC(>15-20), high LH to FSH ratio(>1.5), previous episodes of OHSS, and/or high AMH levels(> 3.36 ng/mL)

SOGC, 2014

Prediction of ovarian response in PCOS= Combination of Prediction of ovarian response in PCOS= Combination of AMH and AFCAMH and AFC

Individualized COH (iCOH) in PCOS:• Improve the cumulative LBR.• Harvesting fertilizable, good quality oocytes.• Cryopreservation of good quality embryos.• Reduce stimulation burden and multiple gestation.• Avoid OHSS.

Optimization of the total reproductive potential Optimization of the total reproductive potential via via embryo cryopreservationembryo cryopreservation should be considered the should be considered the cornerstone targetcornerstone target for for potentiation the success potentiation the success of IVF in of IVF in PCOS.PCOS.

Oehninger et al., 2005

Success for PCOS women undergoing IVF““single live birth single live birth without OHSSwithout OHSS””

Sunkara et al. (2011)

Je et al.(2013)

Baker et al.(2015)

Retrospective400,135 cycles

Large retrospective study SART data analysis231,815 cycles

Increase LBR till 15 retrieved oocytes.

Plateau LBR between 15 and 20 retrieved oocytes.

Declining LBR after 20 retrieved oocytes.

Optimum number of retrieved oocytes is between 6 and 15.

LBR has been increased significantly with the increase in the number of the retrieved eggs.

The more retrieved oocytes associated with significant decrease in the life birth weight.

Pre. COH for IVF workup

Weight loss Metformin Pre ttt with COCs

Which Protocol?!!The starting dose

““Theory of FSH threshold for follicle rescuing”Theory of FSH threshold for follicle rescuing”

Which Protocol?!!The starting dose

Which Protocol?!!The starting dose

““Usual starting dose is 75-150 units of FSH, but Usual starting dose is 75-150 units of FSH, but the total dose of FSH should not exceed 150 the total dose of FSH should not exceed 150

units.”units.”

oLow dose step up protocol. oLow dose step down protocol. oSequential low dose protocol.

Polat et al. , 2014Balasch et al., 2001Hugues et al., 1996

Which Protocol?!!GnRH Agonist For Pituitary Downregulation

Which Protocol?!!GnRH Antagonist For Pituitary Downregulation

Which Protocol?!!Advantages of the Antagonist Downregulation in the Hyperresponders

Simple (with similar pregnancy rates to GnRH agonist-long-down regulation).

Lower incidence of OHSS and cycle cancelation. Give the opportunity to trigger oocyte maturation

using GnRH agonist (prevent OHSS).

““GnRH GnRH antagonistantagonist protocol is protocol is preferredpreferred by many by many programs for COH in the prospective hyperresponders programs for COH in the prospective hyperresponders including PCOS women for the advantage of using including PCOS women for the advantage of using GnRH GnRH agonist triggeragonist trigger for oocyte maturation which for oocyte maturation which preventprevent the development of the development of OHSSOHSS in considerable number of the in considerable number of the high risk women.”high risk women.”

Which Protocol?!!Criteria for triggering of ovulation in COH

More than two follicles measurement was > 17 mm.

Two follicles measurement > 17mm & at least two follicles measurement 15-17 mm.

Premature P4 rise (cutoff point should be 1.5 to 1.7 in the hyperresponders: no consistent agreement !!!).

Can we delay the trigger for one or two days?!!!

GnRH agonist trigger protocolAssiut University IVF Center Experience

1. Trigger: Lucrin 1 mg (20 units) 36 hours prior to planned oocyte retrieval.

2. Measure Progesterone and LH on the day after Lucrin trigger to ensure adequate luteinization.

3. Give hCG 1500IU IM in the recovery room post retrieval.

4. Start estradiol beginning the day after egg retrieval.

5. Start progesterone in oil 50 mg IM daily starting the day after egg retrieval.

6. Continue estradiol and progesterone support till 10 weeks gestation (8 weeks from the day of egg retrieval).

Strategies to prevent OHSSPrimary prevention

Tailoring of personalized stimulation protocol.

Adjuvant agents : Metformin, Cabergoline

Strategies to prevent OHSSSecondary prevention

• Reducing the triggering hCG dose.

• Cycle cancellation.

• Coasting.

• GnRH antagonist downregulation + GnRH agonist trigger (+/- Embryo freezing).

Conclusions

PCOS is challenging and high risk case during COH.

Careful starting dose is a cornerstone part in the success of COH in PCOS.

Antagonist protocol is the best current available option to have the opportunity to prevent OHSS using GnRH agonist trigger.

Aggressive luteal phase support Vs. freeze all strategy should be discussed with the patient when GnRH agonist trigger is used.